• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Structure-function analysis for the induction of pathogenic signaling by H. pylori CagA oncoprotein

Research Project

Project/Area Number 18K07105
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49050:Bacteriology-related
Research InstitutionThe University of Tokyo

Principal Investigator

Hayashi Takeru  東京大学, 大学院医学系研究科(医学部), 助教 (10722209)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords胃がん / ピロリ菌 / CagA / 新規創薬 / 胃発がん
Outline of Final Research Achievements

Helicobacter pylori CagA oncoprotein is closely associated with gastric carcinogenesis. In this study, I succeeded in reconstitution of the complex formation of CagA with multiple human proteins. CagA-SHP2 complex formation was promoted by CagA-PAR1b interaction and, in contrast, suppressed by CagA-Csk interaction, which required homo-dimerization of Csk. Thus, a series of analyses revealed that the CagA interacts with multiple proteins in a more complicated manner than expected. Furthermore, I found small compounds with novel chemical structures that selectively inhibit SHP2 oncoprotein, which is aberrantly activated by CagA.

Academic Significance and Societal Importance of the Research Achievements

ピロリ菌CagAは胃がんに深く関わり、CagAによるヒトタンパク質の脱制御がその病原活性の本態と考えられる。本研究の解析により、CagAが細胞内のPAR1b、SHP2ならびにCskと形成するシグナル撹乱複合体の生化学的性質が新たに明らかになった。また、がんタンパク質として明確な位置づけにあるSHP2は、依然としてその機能に不明な点が多いものの近年創薬の標的としても大きな注目を浴びている。本研究ではSHP2の新たな機能を明らかにするとともに、新規創薬への展開が期待できる結果を得た。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (6 results)

All 2020 2019 2018 Other

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 3 results) Presentation (1 results) (of which Int'l Joint Research: 1 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Alternative splicing reverses the cell-intrinsic and cell-extrinsic pro-oncogenic potentials of YAP12020

    • Author(s)
      Chi Ben, Xiaojing Wu, Atsushi Takahashi-Kanemitsu, Christopher Takaya Knight, Takeru Hayashi, Masanori Hatakeyama
    • Journal Title

      The Journal of Biological Chemistry

      Volume: 295 Issue: 41 Pages: 13965-13980

    • DOI

      10.1074/jbc.ra120.013820

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ピロリ菌の遺伝子多型と胃がん発症リスクを結びつける分子構造解析2019

    • Author(s)
      林剛瑠
    • Journal Title

      日本ペプチド学会ニュースレター

      Volume: 112 Pages: 5-9

    • Related Report
      2019 Research-status Report
    • Open Access
  • [Journal Article] Evaluating the origin and virulence of a Helicobacter pylori cagApositive strain isolated from a non-human primate2018

    • Author(s)
      Kana Hashi, Chihiro Imai, Koji Yahara, Kamrunnesa Tahmina, Takeru Hayashi, Takeshi Azuma, Takako Miyabe-Nishiwaki, Hideyuki Sato, Masao Matsuoka, Sachi Niimi, Munehiro Okamoto, Masanori Hatakeyama
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 15981-15981

    • DOI

      10.1038/s41598-018-34425-4

    • NAID

      120006539613

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Structure-function analysis for deregulation of SHP2 by geographically distinct variants of Helicobacter pylori CagA2018

    • Author(s)
      Takeru Hayashi, Miki Senda, Nobuhiro Suzuki, Chi Ben, Toshiya Senda, Masanori Hatakeyama
    • Organizer
      The 37th Sapporo International Cancer Symposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Book] Photon Factory Highlights 20172018

    • Author(s)
      Takeru Hayashi, Miki Senda, Nobuhiro Suzuki, Toshiya Senda, Masanori Hatakeyama
    • Total Pages
      2
    • Publisher
      High Energy Accelerator Research Organization (KEK)
    • Related Report
      2018 Research-status Report
  • [Remarks] 1つのアミノ酸の違いが日本人胃がん多発の背景に -ピロリ菌の発がん活性を規定する分子構造基盤-

    • URL

      https://www.u-tokyo.ac.jp/focus/ja/articles/a_00617.html

    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi